The etiology of neoplasia is an extremely complex one. A large number of genes have been found to be associated with normal cells being transformed into tumor cells. Genes that have been identified include genes which enhance cell proliferation and suppress cell proliferation. The present view is that it takes more than one mutation event to take a cell from the phenotype of the normal state to the phenotype of the tumor state.
It appears today that human tumors are genetically heterogeneous by the time of clinical presentation, even though they are rather monoclonal in origin. As the tumor progresses, there may be changes in the genome, such as deletions, insertions, substitutions, chromosomal arm exchanges, gene amplification, and the like. These changes may be associated with various characteristics of the cancer, which are important to the diagnosis and therapy of the patient. Information about the cancer, whether it is aggressive, metastatic, or responsive to a particular treatment as a result of particular genomic changes, can greatly aid in the choice of therapy of the patient. For example, more intensive treatment may be warranted for more aggressive cancers.
There is, therefore, substantial interest in identifying specific genetic differences which are associated with neoplastic cells. These differences provide the opportunity to identify groups of patients having analogous lesions, where the course of the cancer may be mapped. In this way, epidemiological data can be adduced as to the nature of the cancer, its response to different therapies, and probable outcomes.
Relevant Literature
Salomon et al. (1991) Science 254:1153 and Lasko et al. (1991) Annu. Rev, Genet. 25:281-314 describe genetic lesions found in tumors. Lisitsyn et al. (a) (1993) Science 259:946-951 describe a method called representational difference analysis (RDA) for analyzing differences between complex but related genomes. See also Lisitsyn et al. (b) (1993) Nature Genetics, 6:57-63. Presti et al. (1991) Cancer Research 51:1544-1552 report loss of at least portions of the Y chromosome in renal cell carcinoma cells. Schwab and Amler (1990) Genes, Chromosomes and Cancer 1:181-193 report the amplification of N-myc in neuroblastoma cells.